孟鲁司特钠联合布地奈德通过p38MAPK通路抑制哮喘炎性反应  

Montelukast sodium combined with budesonide inhibits asthma inflammatory response through the p38MAPK pathway

作　　者：王一迪 朱旭阳 辛子敏 卓馨 江舟[3,4] 汪宇辉[3,4] 成姝婷[3,4] Wang Yi-di;Zhu Xu-yang;Xin Zi-min;Zhuo Xin;Jiang Zhou;Wang Yu-hui;Cheng Shu-ting(West China School of Pharmacy,Sichuan University,Chengdu 610041,China;West China Second University Hospital,Sichuan University,Chengdu 610041,China;West China School of Basic Medical Sciences&Forensic Medicine,Sichuan University,Chengdu 610041,China;Health Ministry Key Laboratory of Chronobiology,Sichuan University,Chengdu 610041,China)

机构地区：[1]四川大学华西药学院,四川成都610041 [2]四川大学华西第二医院,四川成都610041 [3]四川大学华西基础医学与法医学院生物医学工程研究室,四川成都610041 [4]国家卫生健康委员会时间生物学重点实验室(四川大学),四川成都610041

出　　处：《四川生理科学杂志》2024年第1期1-4,8,共5页Sichuan Journal of Physiological Sciences

基　　金：中央高校基本科研业务费专项资金资助(SCU2023D022)。

摘　　要：目的:探究孟鲁司特钠(Montelukast Sodium)联合布地奈德(Budesonide)治疗支气管哮喘(Bronchial Asthma,BA)的效果及机制。方法:选取雄性BALB/C小鼠24只,随机分为空白组、哮喘组、哮喘+孟鲁司特钠组、哮喘+布地奈德组、哮喘+联合给药组,空白组和哮喘组各6只,其余组各4只,除空白组外,其余各组小鼠均按照卵清蛋白(Ovalbumin,OVA)法构建小鼠哮喘模型。建模成功后,对各组小鼠进行相应干预。给药干预结束后,苏木精-伊红(Hematoxylin-Eosin,HE)染色观察比较各组小鼠气道组织形态学变化、酶联免疫吸附法(Enzyme Linked Immunosorbent assay,ELISA)测定支气管肺泡灌洗液(Bronchoalveolar lavage fluid,BALF)中白细胞介素-5(Interleukin-5,IL-5)水平、以及利用蛋白质印迹法(Western blot,WB)肺组织中p38丝裂原活化蛋白激酶(p38 mitogen-activated protein kinase,p38 MAPK)信号通路蛋白表达水平。结果:与空白组相比,哮喘组、哮喘+孟鲁司特钠组、哮喘+布地奈德组、哮喘+联合给药组小鼠气道均出现黏膜组织增厚和明显的炎性细胞浸润,但联合给药组最轻微;与哮喘组相比,哮喘+孟鲁司特钠组、哮喘+布地奈德组、哮喘+联合给药组小鼠肺泡灌洗液IL-5水平均明显降低(P<0.05);而与哮喘+孟鲁司特钠组和哮喘+布地奈德组相比,哮喘+联合给药组小鼠肺泡灌洗液IL-5水平明显降低(P<0.05);哮喘+联合给药组小鼠肺组织中的磷酸化-p38丝裂原活化蛋白激酶(Phospho-p38 MAPK,p-p38MAPK)水平明显低于哮喘+孟鲁司特钠组(P<0.05)。结论:联合给药能够有效改善哮喘的炎性反应的发生及发展,其机制可能与抑制体内p38MAPK磷酸化激活有关。Objective:To investigate the effect and mechanism of montelukast sodium combined with budesonide on bronchial asthma(BA).Methods:A total of 24 male BALB/C mice were selected and randomly divided into control group,model group,montelukast sodium monotherapy group,inhaled budesonide monotherapy group,and montelukast sodium+inhaled budesonide combined therapy group.The control group and model group each had 6 mice,while the other groups had 4 mice.Except for the control group,all other groups of mice were constructed with the OVA method to establish mouse asthma models.After successful modeling,corresponding interventions were performed on each group of mice.After the intervention,hematoxylin eosin(HE)staining was used to observe the morphological changes in the airway tissue of each group of mice;Enzyme linked immunosorbent assay(ELISA)was used to measure the level of Interleukin-5(IL-5)in Bronchoalveolar lavage fluid;Western blot(WB)was used to detect changes in the expression of p38 mitogen-activated protein kinase(p38MAPK)signaling pathway protein in lung tissue.Results:Compared with the Control group,the model group,montelukast sodium monotherapy group,inhaled budesonide monotherapy group,and montelukast sodium+inhaled budesonide combined therapy group all showed mucosal tissue thickening and significant inflammatory cell infiltration in the airway of mice,but the combined therapy group was the least severe;Compared with the Model group,the montelukast sodium monotherapy group,the inhaled budesonide monotherapy group,and the montelukast sodium+inhaled budesonide combined therapy group all showed varying degrees of decrease in IL-5 levels in the alveolar lavage fluid of mice(P<0.01).This indicates that asthma drug therapy can alleviate the disease status of mice by suppressing pulmonary inflammatory reactions;Compared with the monotherapy group of montelukast sodium and the monotherapy group of inhaled budesonide,the combined therapy group of montelukast sodium and inhaled budesonide significantly reduced the le

关 键 词：孟鲁司特钠 布地奈德 联合给药 哮喘 P38MAPK 

分 类 号：R562.25[医药卫生—呼吸系统]